Juvenile Idiopathic Arthritis

Disease/Disorder

Definition

Juvenile idiopathic arthritis (JIA), previously known as juvenile rheumatoid arthritis (JRA) or juvenile chronic arthritis (JCA) is a form of arthritis (i.e., joint swelling or limitation in range of movement with associated warmth, pain or tenderness) of unknown etiology that occurs for at least 6 weeks in children younger than 16 years of age.¹ Thought to be a multifactorial autoimmune disease with unknown exact cause, it can continue into adulthood, causing significant disability, poor functional outcomes, and decreased quality of life.²

Etiology

Current research indicates that genetic, immunogenic, and environmental factors influence the development of JIA and varies between disease subtypes. Non-systemic variations of JIA are more likely to be associated with the human leukocyte antigen (HLA) class.^3,4 HLA-A2 & HLA-B27 are implicated in certain forms of JIA, especially in subtypes with earlier onset.

In addition to HLA genetic associations, non-HLA genes also play a role in the inflammatory response in certain JIA subtypes, with involvement of both humoral and cell-mediated immunity. Multiple genes relating to inflammation and immune regulation are believed to be involved, including those that influence TNF, IL2, IL10, IL6 and other inflammatory regulators.² There is evidence of autoimmune dysregulation, with positive antinuclear antibody (ANA) in 40% of patients; however, evidence from treatments designed to block the inflammatory cascade indicate that systemic inflammation may play a greater role.

Most recently, a study identified several novel genes that may be implicated in the development of disease, ANXA3, GPR146, ANKRD9, and TMEM158. While this has improved our understanding of genetic correlations with disease development, conclusive causation remains under investigation.⁴

Patho-anatomy/physiology

JIA is an inflammatory syndrome characterized by chronic synovial inflammation with B-lymphocytes. Macrophage and T-lymphocyte invasion occur along with cytokine release and further synovial proliferation. There is a major pathogenic role for the overproduction of interleukin-6 and interleukin-1.^2,6 Eventually, the thickened synovium (pannus) contributes to joint destruction. Within the synovial fluid itself, interleukin-18 expression has consistently been found to be abnormal.

The subtypes of juvenile arthritis can be differentiated from one another based on the number of affected joints, underlying biochemistry, and the presence of associated comorbidities. Subtypes are classified using the International League of Associations for Rheumatology (ILAR).

JIA Subtypes^1,5,6

• Oligoarticular
  • Persistent oligoarthritis: affecting fewer than four joints throughout the course of the disease
  • Extended oligoarthritis: affecting two to four joints during first six months of disease, but greater than five joints after six months of disease
  • ANA + lab result in 70-80% of patients
  • Onset: early childhood (under 6 years old), Females > Males
  • Most common subtype with 40-50% of cases¹
  • Larger lower extremity joints, especially knees (most commonly affected)
  • Often with asymmetric arthritis presentation
  • Asymmetric uveitis often develops within first four years
    • Requires routine eye examinations
  • Ocular damage common, 50% develop chronic iridocyclitis
  • Overall best prognosis
• Polyarticular
  • Affects five or more joints during the first six months of disease
    • Symmetric involvement of small joints of hands and feet
    • Cervical spine and temporomandibular joint (TMJ) may be affected
  • Two subtypes
    • Rheumatoid factor (RF) negative polyarthritis: More often, patients complain of stiffness versus pain
      • Typically presents with symmetric small joint involvement and severe inflammation
        • Hip involvement 50% of cases can lead to late disability with erosion of the femoral head
      • 18-30% of JIA patients
      • Positive ANA in 20-40% of RF negative polyarthritis
    • RF positive polyarthritis: Less than 5% of all JIA cases, with 50% developing severe arthritis
      • Variable prognosis due to more aggressive disease course
      • May have positive antibodies to cyclic citrullinated peptides (anti-CCP)⁸
  • ANA+ in 25%-40% of cases
  • Onset: RF positive in late childhood, RF usually negative in younger than six years; Females > Males
• Systemic: formerly Still’s Disease or systemic juvenile rheumatoid arthritis
  • Arthritis in one or more joints with, or preceded by, fever of at least two weeks duration and daily fever (at least three days).
  • Further accompanied by at least one of the following signs
    • Non-fixed erythematous skin rash
      • Macular rash, evanescent, salmon colored
      •  Accompanies fever
    • Generalized lymph node enlargement, hepatomegaly, or splenomegaly
    • Serositis
  • 5-8% of children develop macrophage activation syndrome (MAS)¹
    • Secondary to uncontrolled activation and proliferation of T-lymphocytes and macrophages.
    • Life-threatening condition resulting in persistent fever, pancytopenia, hepatosplenomegaly, and coagulopathy.
    • Treatment focuses on high dose steroid therapy or immunosuppressive therapy
  • 10% of JIA patients
  • Onset: any age, Female = Males
    • 10%-20% develop acute iridocyclitis
  • Arthritis occurs later
• Psoriatic
  • Arthritis and psoriasis with at least two of the following
    • Dactylitis
    • Nail pitting or onycholysis
    • Psoriasis in a first-degree relative
  • 5-10% of patients
  • Onset: biphasic with early peak younger than six years, late peak after six years of age, females=male
• Enthesitis-Related
  • Enthesitis at the sites of tendon insertion on to bone with at least two of the following
    • Presence or history of sacroiliac joint tenderness or lumbosacral pain
    • HLA-B27 antigen positive
    • Onset of arthritis in male over six years of age
    • Acute symptomatic anterior uveitis
    • History of ankylosing spondylitis
    • Enthesitis-related arthritis
    • Sacroiliitis with inflammatory bowel disease
    • Acute anterior uveitis (Reiter’s syndrome) in a first-degree relative
  • Occurs in 15-20% of JIA patients
  • Most common sites: calcaneal insertion of Achilles tendon, plantar fascia, tarsal area
  • Most common age of onset is 10 years of age
  • Complications include
    • Sacroiliac joint involved in 30-40% of patients with this type of JIA
    • Uveitis is common: often symptomatic and unilateral
    • Can progress to spondyloarthropathy
  • Onset: late childhood, commonly after 6 years old, Males > Females
    • Positive Family Medical History may be present
• Undifferentiated
  • 5% of JIA subtypes
  • Male=Female
  • May meet none or many of the criteria of other JIA subtypes

Essentials of Assessment

History

• Joint pain and swelling, often noted incidentally after trauma
• Stiffness worse in morning or after naps and lasts more than fifteen minutes
• Symptoms better later in the day
• Persistence of symptoms for at least six weeks in a six-month period
• History of fever without other cause, in absence of joint symptoms; may be three days, with a double spike pattern of high temperatures
• Child refusing to walk, or using hands to walk
• Pain with ambulation, “gelling” sensation (stiffness after a joint remains in one position for a prolonged period), joint swelling, and difficulty with buttons or writing
• Photophobia, pain, redness, headache, and visual changes
• Isolated musculoskeletal pain is generally not JIA
• Detailed family medical history^1,7

Differential diagnoses include: Perthes disease, slipped capital femoral epiphysis (SCFE), malignancy (osteosarcoma for joint pain, leukemia for fever combined with joint pain, lymphoma), ankylosing spondylitis, inflammatory bowel disease, septic arthritis, Kawasaki disease, malaria.

Physical examination

• Musculoskeletal
  • Painful, swollen joints; tenosynovitis>bursitis
  • Number of joints
    • 2-4: Oligoarticular
    • 5 or more: Polyarticular
    • Any joint can be affected, including small joints of the fingers, sternocostal, vertebral joints (including cervical), and the jaw. Knees, wrists, and ankles are more affected in polyarticular.
    • Note if deformity presents with chronic disease.
  • Range of motion: May be decreased or contractures may be present. May see cervical spine involvement
• Extremities: limb length discrepancy. Lymphadenopathy possible in systemic disease. Children are more likely to present with ulnar deviation and loss of extension. Radial deviation may occur at the MCP joints with finger flexion
• Gait: antalgic limp
• Head, eyes, neck: Uveitis in girls with positive ANA and oligoarticular JIA. Receding chin from early ossification of the mandible (micrognathia)
• Skin: evaluate for rashes. Document type and location.
• Gastrointestinal: systemic disease may have hepatomegaly and/or splenomegaly
• Cardiovascular: may have pericarditis, myocarditis (muffled heart sounds, pericardial friction rub)

Laboratory studies

No specific laboratory studies diagnose JIA. Blood testing for inflammatory markers (Erythrocyte sedimentation rate, C-reactive protein) and autoimmune markers (RF, HLA-B27, ANA) are recommended.

• RF-positive in 3%-5% of polyarticular subtype
•  ANA positive in 80% of oligoarticular subtype, associated with uveitis
•  Serial trending of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) help gauge effectiveness of treatment
•  Complete blood count (CBC) to evaluate for anemia of chronic disease and leukocytosis
• Joint aspiration to rule-out septic arthritis

Imaging

Plain films, magnetic resonance imaging (MRI), and ultrasound can be used to detect joint changes.

• Plain films: periarticular soft tissue swelling, overgrown or ballooned epiphyses, periostitis
  • Later, may show erosive disease, joint space loss
  • Periarticular bone demineralization radiographically once at 50% demineralization
• MRI: high sensitivity to detect bone damage and damaged cartilage
• Ultrasound: Noninvasive tool useful for assessing number of joints involved and differentiating between tendon and articular involvement without radiation⁷
• Dual-energy x-ray absorptiometry (DEXA): to identify osteoporosis

Rehabilitation Management and Treatments

Available or current treatment guidelines

• 2019 American College of Rheumatology Recommendations for the Treatment of Juvenile Idiopathic Arthritis
  • 2021 guideline updates provided for several types of JIA⁶
• 2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis Recommendations for Nonpharmacologic Therapies, Medication Monitoring, Immunizations, and Imaging⁹
• American College of Rheumatology Guideline for the Treatment of JIA Oligoarthritis, TMJ, sJIA Guideline, 2021¹⁰

At different disease stages

New onset/acute

• Early intervention focuses on symptom relief through medication and physiotherapy and adopting adequate lifestyle changes.
  • Rest, Splinting, Passive Range of Motion (ROM), Strengthening Exercises, Adaptive Equipment, Functional Training
• First-line medications
  • Non-steroidal anti-inflammatory drugs (NSAIDs) for pain and decrease of inflammation (typically see improvement in first 1-3 days)¹¹
    • Diclofenac
    • Naproxen
    • Ibuprofen
    • Indomethacin
    • Meloxicam
    • Tolmetin
  • Intra-articular steroid injections with triamcinolone hexacetonide is preferred for children
  • For uveitis, topical corticosteroids followed by systemic corticosteroids or biologics in resistant cases (such as Infliximab)
• Second-line medications in cases of more severe or refractory acute disease presentation:
  • Include patients with systemic symptoms or severe onset in the acute setting
  • Poor response to NSAIDs
  • IL-6 or IL-1 inhibitors
    • Anakinra
    • Canakinumab
    • Tocilizumab
  • Methotrexate
  • Glucocorticoids: although systemic steroids are being used less frequently in acute settings, refractory or severe cases may still benefit from addition of systemic glucocorticoid use
• Includes rehabilitation strategies that stabilize or optimize function and prepare for further interventions at later disease stages:
  • Gentle range of motion
  • Cold packs applied to joints
  • Supportive orthoses, especially knees and wrists to maintain alignment
  • Shoe modifications to support ankles and feet
  • Appropriate physical activity, based on symptom burden
    • Low-impact activities may be beneficial and less aggravating
      • Swimming or cycling
  • Appropriate rest from activities during flares

Subacute

• In ongoing therapy, the treatment remains focused on symptom management through medication and physiotherapy and lifestyle modifications.¹¹
• First line therapy:
  • Disease-Modifying Antirheumatic Drugs (DMARDs)
    • Methotrexate
    • Sulfasalazine: helpful in enthesitis-related disease⁹
  • Anti–interleukin (IL)-1 agents include anakinra, canakinumab, rilonacept
  • Anti–IL-6 agent tocilizumab
• Second line therapy
  • TNF-α inhibitors like etanercept, infliximab, and adalimumab help reduce flare-ups
    • Repeated annual screening of TB in low-risk patients with a negative initial TB screen is not recommended
  • T-cell immunologic medications such as abatacept¹¹
  • CD-20 antigen suppression agent Rituximab⁸
  • Anti-tumor necrosis factor drugs in addition to those above
    • May have severe adverse effects, requiring dose adjustments
  • Systemic corticosteroids are becoming less used in initial management of JIA flare ups, reserved for resistant cases^9,11
    • Should be monitored closely as long term steroid use can be detrimental
• Includes rehabilitation strategies to optimize function:
  • Range of motion: passive ROM exercises should NOT be performed in an inflammatory joint
  • Cold: pain relief, increase pain threshold, decrease muscle spasm (vasoconstriction)
  • Heat, including paraffin and beads for hands
    • Increases tissue elasticity, reduces stiffness, decreases pain, reduces muscle spasm
    • Superficial heat (hot pack) can provide tissue heat up to one centimeter in depth¹
  • Hydrotherapy: Water temperature between 90-100 degrees Fahrenheit
  • Ultrasound modality generally avoided in children due to controversy over growth-plates
  • Mobilization to prevent debility
  • Joint protection techniques
    • Splinting of the upper extremity: 15-20 degrees of wrist extension, finger flexion, 25% MCP flexion. It is important to control ulnar deviation and thumb abduction¹
  • Adaptive equipment for mobility (walker with forearm supports if grip is too difficult) and ADLs (adapted silverware, pencil or crayons)
  • Adapted computer access

Chronic/stable

• Includes secondary prevention and disease management strategies
  • Monitor cervical spine
  • Supportive orthotics, especially for knees, feet, ankles, and wrists
  • Jaw guards for sports if jaw involved
• Includes palliative strategies
  • Supportive nutrition
• Includes symptom relief
  • NSAIDs
  • Appropriate and adequate pain management
  • Complementary and alternative medicine techniques common
• Includes rehabilitation strategies to optimize function
  • Massage
  • Stretching and flexibility
  • Yoga
  • Exercise program including aquatics
    • Aerobics, while protecting joints
    • Strengthening, isometrics may be better for affected joints
  • Participation in sports is not contraindicated
  • Joint protection strategies
  • Environmental adaptations
  • Nighttime resting splints

Future Directions

Updated ACR guidelines for the treatment of JIA were discussed at the 2026 Rheumatology Winter Clinical Symposium and are expected to be published later in 2026. These new guidelines emphasize earlier, more aggressive treatment. They include 15 new recommendations for systemic JIA and 33 new recommendations for non-systemic JIA. New guidelines recommend decreased reliance on NSAIDs and glucocorticoids. Instead, earlier introduction of DMARDs is recommended with a preference for oral methotrexate.¹³

References

1. Cuccurullo, Sara J. Physical Medicine and Rehabilitation Board Review. Fourth Edition. Demos Medical. 2020. 753-759
2. Zaripova, L.N., Midgley, A., Christmas, S.E. et al. Juvenile idiopathic arthritis: from aetiopathogenesis to therapeutic approaches. Pediatr Rheumatol 19, 135 (2021). https://doi.org/10.1186/s12969-021-00629-8
3. De Silvestri A, Capittini C, Poddighe D, Marseglia GL, Mascaretti L, Bevilacqua E, et al. HLA-DRB1 alleles and juvenile idiopathic arthritis: diagnostic clues emerging from a meta-analysis. Autoimmun Rev. 2017;16(12):1230–6.
4. Feng R, Lu M, Yin C, Xu K, Liu L, Xu P. Identification of candidate genes and pathways associated with juvenile idiopathic arthritis by integrative transcriptome-wide association studies and mRNA expression profiles. Arthritis research & therapy. 2023;25(1):19. doi:10.1186/s13075-023-03003-z
5. Clarke, S.L.N., Richmond, R.C., Zheng, J., Spiller, W., Ramanan, A.V., Sharp, G.C. and Relton, C.L. (2022), Examining Health Outcomes in Juvenile Idiopathic Arthritis: A Genetic Epidemiology Study. ACR Open Rheumatology, 4: 363-370. https://doi.org/10.1002/acr2.11404
6. Hinze, C.H., Foell, D. & Kessel, C. Treatment of systemic juvenile idiopathic arthritis. Nat Rev Rheumatol 19, 778–789 (2023). https://doi.org/10.1038/s41584-023-01042-z
7. Kaeley, G.S., Bakewell, C. & Deodhar, A. The importance of ultrasound in identifying and differentiating patients with early inflammatory arthritis: a narrative review. Arthritis Res Ther 22, 1 (2020). https://doi.org/10.1186/s13075-019-2050-4
8. Viola S, Felici E, Magni-Manzoni S. Development and Validation of a Clinical Index for Assessment of Long-Term Damage in Juvenile Idiopathic Arthritis. Arthritis & Rheumatism. 2005;52(7):2092-2102.
9. Onel KB, Horton DB, Lovell DJ, Shenoi S, et al. 2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Recommendations for Nonpharmacologic Therapies, Medication Monitoring, Immunizations, and Imaging. Arthritis Care Res (Hoboken). 2022 Apr;74(4):505-520. doi: 10.1002/acr.24839. Epub 2022 Mar 1. PMID: 35233989.
10. Onel KB, Horton DB, Lovell DJ, Shenoi S, et al. 2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Recommendations for Nonpharmacologic Therapies, Medication Monitoring, Immunizations, and Imaging. Arthritis Care Res (Hoboken). 2022 Apr;74(4):505-520. doi: 10.1002/acr.24839. Epub 2022 Mar 1. PMID: 35233989
11. PediaMCU. 2022. Juvenile Idiopathic Arthritis: Treatment Algorithm. Cairo University Specialty Pediatric Hospital. Accessed on April 10, 2023. https://pediamcu.com/18/
12. Iversen MD, Andre M, von Heideken J. Physical Activity Interventions in Children with Juvenile Idiopathic Arthritis: A Systematic Review of Randomized Controlled Trials. Pediatric Health Med Ther. 2022 Apr 14;13:115-143. doi: 10.2147/PHMT.S282611. PMID: 35444485; PMCID: PMC9015041.
13. Kilgore, C. (2026, March 6). Pediatric rheumatologist explains many new updates to ACR’s juvenile idiopathic arthritis guidelines. Medscape.

Original Version of the Topic

Edward Hurvitz, MD. Juvenile Idiopathic Arthritis. 11/10/2011

Previous Revision(s) of the Topic

Todd R. Lefkowitz, MD, Sean Bemanian, MD Juvenile Idiopathic Arthritis. 4/21/2016. 

Glendaliz Bosques, MD, Mani P. Singh, MD. Juvenile Idiopathic Arthritis. 7/28/2020.

Olivia Tincher, Cristina Marie Sanders, DO, Rajashree Srinivasan, MBBS. Juvenile Idiopathic Arthritis. 6/14/2023.

Author Disclosure

Cristina Marie Sanders, DO, MS
Nothing to Disclose

Olivia Tincher, DO
Nothing to Disclose

Rajashree Srinivasan, MBBS
Nothing to Disclose

Cooper Deupree, MS IV
Nothing to Disclose